SELINEXOR for Diffuse large B-cell lymphoma (DLBCL) | Relapsed/refractory diffuse large B-cell lymphoma

Inclusion criteria

• {"criterion_text":"- Patients ≥18 years of age\n- An estimated life expectancy of >3 months at Screening\n- Patients with primary refractory DLBCL defined as no response or relapse within 6 months after ending first-line treatment will be allowed on study\n- Agree to highly effective contraception during the duration of the study with contraception use continuing for 12 months after the last dose of study treatment • Female patients of childbearing potential must have a negative serum pregnancy test at Screening and agree to use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment (except patients with non-childbearing potential: Age >50 years and naturally amenorrhoeic for >1 year, or previous bilateral salpingo-oophorectomy, or hysterectomy). • Male patients who are sexually active must use highly effective methods of contraception throughout the study and for 12 months following the last dose of study treatment. Male patients must agree not to donate sperm during the study treatment period and for 12 months following the last dose of study treatment.\n- Have pathologically confirmed de novo DLBCL or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). Patients with high grade lymphoma with c-MYC, Bcl-2 and/or Bcl-6 rearrangements are eligible (Phase 2 only) (Documentation to be provided)\n- Have received at least 1 but no more than 3 prior lines of systemic therapy for the treatment of DLBCL with relapsed or refractory disease following their most recent regimen (Documentation to be provided) • Salvage chemoimmunotherapy followed by stem cell transplantation will be considered as 1 line of systemic therapy • Maintenance therapy will not be counted as a separate line of systemic therapy • Radiation with curative intent for localized DLBCL will not be counted as 1 line of systemic therapy\n- Positron emission tomography (PET) positive measurable disease with at least 1 node having longest diameter (LDi) >1.5 cm or 1 extranodal lesion with LDi >1 cm (per the Lugano 2014 Criteria) (Documentation to be provided). The Deauville 5-point scale (D5PS) score assessed on the FDG PET/CT should be between 3 to 5.\n- Not intended for HSCT or CAR-T cell therapy based on objective clinical criteria determined by the treating physician. Patients who cannot receive HSCT due to active disease are allowed on study (up to approximately 15% of patients enrolled in each Phase). Documentation on lack of intention to proceed to receive HSCT or CAR-T therapy must be provided by the treating physician.\n- Adequate bone marrow function at screening, defined as (Documentation to be provided): • Absolute neutrophil count ≥1 × 109/L • Platelet count ≥100 × 109/L (without platelet transfusion <14 days prior to C1D1) • Hemoglobin ≥8.5g/dl (without red blood cell transfusion <14 days prior to C1D1)\n- Circulating lymphocytes ≤50 × 109/L\n- Adequate liver and kidney function, defined as (Documentation to be provided): • Aspartate transaminase (AST) or alanine transaminase (ALT) ≤2.5 × upper limit of normal (ULN), or ≤5 × ULN in cases with known lymphoma involvement in the liver • Serum total bilirubin ≤2 × ULN, or ≤5 ULN if due to Gilbert syndrome or in cases with known lymphoma involvement in the liver • Calculated creatinine clearance (CrCl) ≥30 mL/min based on Cockcroft-Gault formula\n- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2"}

Exclusion criteria

• {"criterion_text":"- DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma; composite lymphoma (Hodgkin’s lymphoma + non-Hodgkin’s lymphoma [NHL]); DLBCL transformed from diseases other than indolent NHL; primary mediastinal (thymic) large B-cell lymphoma (PMBL); T-cell rich large B-cell lymphoma.\n- Previous treatment with selinexor or other XPO1 inhibitors\n- Contraindication to any drug contained in the combination therapy regimen (SR-GDP)\n- Known active central nervous system or meningeal involvement due to DLBCL at the time of Screening\n- Use of any standard or experimental anti-DLBCL therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) <21 days prior to Cycle 1 Day 1 (Prednisone <30 mg or equivalent are permitted; palliative radiation is permitted only if on non-target lesions)\n- Any AE, by Cycle 1 Day 1, which has not recovered to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] v5.0), or returned to baseline, related to the previous DLBCL therapy, except hematological abnormalities (per Inclusion criteria #6) and alopecia\n- Major surgery <14 days of Cycle 1 Day 1\n- Hematopoietic stem cell transplantation/CAR-T therapy as follows: • Autologous HSCT <100 days or allogeneic HSCT <180 days prior to Cycle 1 Day 1 • Active graft-versus-host disease (GVHD) after allogeneic HSCT (or cannot discontinue GVHD treatment or prophylaxis) • CAR-T infusion <90 days prior to Cycle 1\n- Neuropathy Grade ≥2 (CTCAE v5.0)\n- Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator’s opinion, could compromise the patient’s safety, or being compliant with the study procedures\n- Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within 7 days prior to first dose of study treatment; however, prophylactic use of these agents is acceptable (including parenteral)\n- Patients with active hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infections: • Patients with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 IU/mL prior to first dose of study treatment. • Patients with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. • Patients with HIV are allowed if they have a negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year.\n- Inability to swallow tablets, malabsorption syndrome, or any other gastrointestinal disease or dysfunction that could interfere with absorption of study treatment\n- Breastfeeding or pregnant women\n- Inability or unwillingness to sign an informed consent form (ICF)\n- In the opinion of the Investigator, patients who are significantly below their ideal body weight\n- Patients who received a live attenuated vaccine within prior 28 days of the first dose of study treatment"}

Primary endpoints

• {"endpoint_text":"- Phase 2: overall response rate (ORR) based on the Lugano Classification 2014.","definition_or_measurement_approach":"ORR assessed according to the Lugano 2014 Criteria (response evaluation by PET/CT and Deauville 5-point scale as per protocol)."}
• {"endpoint_text":"- Phase 3: Progression-free survival (PFS) based on the Lugano Classification 2014","definition_or_measurement_approach":"PFS defined and measured per the Lugano 2014 Criteria (time from randomisation to documented progression or death)."}

Secondary endpoints

• {"endpoint_text":"- Phase 2: Progression-free survival (PFS) based on the Lugano Classification 2014. Overall survival","definition_or_measurement_approach":"PFS and overall survival (OS) measured per protocol; PFS per Lugano 2014; OS = time from randomisation to death from any cause."}
• {"endpoint_text":"- Phase 3: overall response rate (ORR) based on the Lugano Classification 2014. Overall survival.","definition_or_measurement_approach":"ORR assessed per Lugano 2014; OS = time from randomisation to death from any cause."}

Italy

Earliest CTIS Part Ii Submission Date

24-07-2024

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

111

Number Of Sites

6

Number Of Participants

27

Spain

Earliest CTIS Part Ii Submission Date

24-07-2024

Latest Decision Or Authorization Date

07-11-2024

Processing Time Days

106

Number Of Sites

3

Number Of Participants

18

Poland

Earliest CTIS Part Ii Submission Date

24-07-2024

Latest Decision Or Authorization Date

08-11-2024

Processing Time Days

107

Number Of Sites

3

Number Of Participants

15

Primary sponsor

Full Name

Karyopharm Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Drugdev Inc.

Responsibilities

Site Payment

Name

Almac Clinical Services Limited

Name

Eclinical Solutions LLC

Name

4g Clinical LLC

Name

PPD (UK) Limited

Name

AIT Bioscience, LLC

Name

Labconnect LLC

Name

WCG Clinical Inc.

Name

Intana Bioscience GmbH

Name

Precision for Medicine (HU) Kft.

Third parties

• {"country":"United States","full_name":"Drugdev Inc.","duties_or_roles":"Site Payment","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eclinical Solutions LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"PPD (UK) Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"AIT Bioscience, LLC","duties_or_roles":"","organisation_type":"Industry"}
• {"country":"United States","full_name":"Labconnect LLC","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"WCG Clinical Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Intana Bioscience GmbH","duties_or_roles":"","organisation_type":"Industry"}
• {"country":"Hungary","full_name":"Precision for Medicine (HU) Kft.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}